Effects of Standard-Dose Prophylactic, High-Dose Prophylactic, and Therapeutic Anticoagulation in Patients With Hypoxemic COVID-19 Pneumonia
Authors: Vincent Labbé, Damien Contou, Nicholas Heming, Bruno Megarbane, Keyvan Razazi, Florence Boissier, Hafid Ait-Oufella, Matthieu Turpin, Serge Carreira, Alexandre Robert, Mehran Monchi, Bertrand Souweine, Sebastien Preau, Denis Doyen, Emmanuel Vivier, Noémie Zucman, Martin Dres, Mohamed Fejjal, Elise Noel-Savina, Marwa Bachir, Karim Jaffal, Jean-François Timsit, Santiago Alberto Picos, Eric Mariotte, Nihal Martis, William Juguet, Giovanna Melica, Paul Rondeau, Etienne Audureau, Armand Mekontso Dessap, Gaetan Plantefevre, Djillali Annane, Aurélien Dinh, Lilia Abdeladim, Rania Bounab, Pierre Moine, Virginie Maxime, Hayette Tessa, Miguel Carlos, Emmanuelle Kuperminc, Sebastian Voicu, Isabelle Malissin, Nicolas Deye, Aymen M'Rad, Thomas Lacoste-Palasset, Thomas Lefevre, Luc Haudebourg, Jean-Michel Ekhérian, François Bagate, Nicolas de Prost, Guillaume carteaux, Inès Bendib, Samuel Tuffet, Julien Lopinto, Pascale Labedade, Gaêl Michaud, Brice Benelli, Anne Fleur Haudebourg, Ségolène Gendreau, Enora Berti, Astrid Bertier, Romain Arrestier, Paul Masi, Etienne Dufranc, Remi Coudroy, Arnaud W Thille, Anne Veinstein, Delphine Chatellier, Jean-Pierre Frat, Maeva Rodriguez, Faustine Reynaud, Victor De Roubin, François Arrive, Paul Gabarre, Diane Bollens, Patrick Ingiliz, Benedicte Lefebvre, Zineb Ouazene, Thibault Chiarabini, Nadia Valin, Tomas Urbina, Vincent Bonny, Naike Bige, Karine Lacombe, Muriel Fartoukh, Cyrielle Desnos, Guillaume Voiriot, Michel Djibré, Clarisse Blayau, Aude Gibelin, Julien Dessajan, Ludovic Lassel, Pierre-Marie Bertrand, Raphael Chambon, Nicolas Clément, Oumar Sy, Sebastien Jochmans, Claire Dupuis, Laure Calvet, François Thouy, Kevin Grapin, Guillaume Laurichesse, Frederic Kinda, Pierre Couhault, Loïc Dopeux, Julien Goutay, Geoffrey Ledoux, Romain Tortuyaux, Alexandre Gaudet, Anahita Rouze, Anne-Sophie Moreau, Patrick Girardi, Mercedes Jourdain, Julien Poissy, Raphael Favory, Saadala Nseir, Matthieu Buscot, Jean Dellamonica, Clément Saccheri, Elisa Demonchy, David Chirio, Karine Risso, Nihal Martis, Marina Taurel, Gaël Bourdin, Pierre Donze, Christian Pommier, Sylvène Rosselli, Marine Simonin, Jean-Damien Ricard, Ingrid Thiry, Santiago Freita ramos, Charles Verney, Fabrice Uhel, Isabelle Priour, Damien Roux, Alexandra Beurton, Côme Bureau, Robin Déléris, Julien Mayaux, Julien Le Marec, Safaa Nemlaghi, Sébastien Clerc, Aleandre Demoule, Elise Morawiec, Benjamin Picard, Jérémie Pichon, Pierre Chafiotte, Sophie Menat, Sandrine Pontier, Frédérique Legenne, Lila Bouadma, Moustafa Abdel-Nabey, Tiphaine Girard, Pierre Jaquet, Juliette Patrier, Simona Presente, Julien Leroy, Frederic Mechai, Hugues Cordel, Nolan Hassold-Rugolino, Malo Emery
Journal: JAMA Internal Medicine (2023)

Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative.To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies.The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis-114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023.Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days.A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death).Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, -14.7 [95% CI -6.2 to -23.2] and -14.7 [95% CI -6.2 to -23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, -13.5; 95% CI -2.6 to -24.3).This randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis.ClinicalTrials.gov Identifier: NCT04808882.